Catabolism refers to the metabolic pathways that break down molecules such as polysaccharides, nucleic acids, lipids and proteins into smaller units, while anabolism refers to the metabolic pathways that construct molecules from smaller units. Catabolism produces energy, while anabolism requires energy. The catabolic state refers to the condition wherein the body uses stores of carbohydrates, amino acids, or fats as a source of energy for maintenance, thereby generating urinary nitrogen and CO2 in breath. These changes will show up quickly in urine and breath. Body carbohydrates, amino acids, and fats are also a source of nutrients to synthesize defense products, e.g., immunoglobulins and acute phase proteins, which can be a function of the catabolic state. Hence, there can be concomitant anabolic processes occurring in an organism even during a general state of catabolism. The catabolic state may be induced by infection, disease, external pathogens, toxic chemical exposure, malnutrition, or other causes. Early detection of the onset of the catabolic state, as an indicator of a serious disease, has broad applications in human and veterinary health. In sepsis alone, the mortality rate of 44% (among 750,000 reported cases) can be cut in half through earlier detection and intervention.
A noninvasive, non-doping, rapid stable isotope method to discern the onset of the catabolic state by detecting isotopic changes in the exhaled CO2 in breath was described in issued U.S. Pat. No. 5,912,178 (the '178 patent). The relative health of an organism was determined by comparing the sampled ratio (C13:C12) to a baseline ratio in the organism by testing breath samples in a mass spectrometer, for example. The methods disclosed in the '178 patent allow for a non-invasive determination of net catabolic processes of organisms experiencing altered organ function or a deficit in nutrient intake. One disadvantage to the method disclosed in the '178 patent is that a comparison specimen is required to determine if the organism from which a breath sample is measured is in a catabolic state.
Similarly, in U.S. Pat. No. 7,465,276 (the '276 patent), the relative amounts of first and second breath isotopes are measured over time to determine if an organism is experiencing a viral or bacterial infection. Advantages of the method of the '276 patent are that breath samples from an isotopically unenriched organism can be monitored for changes in isotope ratios over time to determine if the organism is experiencing a bacterial or viral infection. A disadvantage of the method is that a baseline measurement from the healthy subject is preferred so that changes from the baseline can be measured that are indicative of infection. In addition, it is generally advisable to obtain measurements over several hours or even several days so that the change in isotope ratio from the baseline ratio can be determined. Thus, determining the transition from a healthy to an infected organism within the short-term infection period, e.g., 30 minutes to 2 hours, may not be possible as the change in slope may not be measurable in this time period.
What is needed are additional methods to use the changes in isotope ratios in breath to determine the catabolic or infected state of an organism as well as the transition from healthy to sick to allow for prompt therapeutic intervention.